The Effects of H2S on the Activities of CYP2B6, CYP2D6, CYP3A4, CYP2C19 and CYP2C9 in Vivo in Rat

Hydrogen sulfide (H₂S) is a colorless, flammable, extremely hazardous gas with a “rotten egg” smell. The human body produces small amounts of H₂S and uses it as a signaling molecule. The cocktail method was used to evaluate the influence of H₂S on the activities of CYP450 in rats, which were reflected by the changes of pharmacokinetic parameters of five specific probe drugs: bupropion, metroprolol, midazolam, omeprazole and tolbutamide, respectively. The rats were randomly divided into two groups, control group and H₂S group. The H₂S group rats were given 5 mg/kg NaHS by oral administration once a day for seven days. The mixture of five probes was given to rats through oral administration and the blood samples were obtained at a series of time-points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by LC-MS. In comparing the H₂S group with the control group, there was a statistically pharmacokinetics difference for midazolam and tolbutamide; the area under the plasma concentration-time curve (AUC) was decreased for midazolam (p < 0.05) and increased for tolbutamide (p < 0.05); while there was no statistical pharmacokinetics difference for bupropion, metroprolol and omeprazole. H₂S could not influence the activities of CYP2B6, CYP2D6 and CYP2C19 in rats, while H₂S could induce the activity of CYP3A4 and inhibit the activity of CYP2C9 in rats.     

Influence of CYP1A2 and NAT2 Metabolic Phenotypes on Smokers' Urinary Mutagenicity

The influence of the metabolic phenotypes NAT2 and CYP1A2 on urinary mutagenicity of 118 smokers was studied. Mutagenicity of urine samples was determined by Ames test (preincubation plate incorporation assay on YG1024 Salmonella typhimurium strain with S9 mix). Urinary nicotine plus its metabolites were determined to check cigarette smoke intake. The N -acetyltransferase (NAT2) and cytochrome P450 1A2 (CYP1A2) phenotypes were measured by the molar ratio of urinary caffeine metabolites, determined by HPLC analysis. Urinary mutagenicity was significantly higher in smokers CYP1A2 extensive (EM) than in CYP1A2 poor metabolizers (PM) (Mann-Whitney U test, p = 0.020). Linear multiple regression analysis shows that an increase in urinary mutagenicity levels was significantly related to cigarette smoke intake and to CYP1A2 N -hydroxylation activity ( t = 5.06, p < 0.001, and t = 2.33, p = 0.021), but not to NAT2 acetylation phenotype. In conclusion, phenotypic differences in metabolic activation of tobacco smoke mutagens are able to modulate the presence of mutagens in urine of cigarette smokers and, consequently, the potential genotoxic risk.     

The influence of the alite polymorphism on the strength of the Portland cement

The influence of the alite polymorphism on the strength of cement was monitored in a set of laboratory-prepared clinkers with equal quantitative phase composition and different ratio of modifications. The alite polymorphism in clinkers was influenced by the change of the MgO and SO₃ side oxides in clinker, raw meal reactivity change, raw meal preheating, burning temperature or by the adding of crystallisation nuclei. The differences in the hydraulic properties of the M₁ and M₃ modifications were determined. In the case of all the hydration periods monitored, the strength of cements with the M₁ modification was 10% higher than the strength of cements with the M₃ modification.     

The influence of chemical interesterification on the physicochemical properties of complex fat systems. 2. Morphology and polymorphism

Palm oil-soybean oil (POSBO) blends and lard-canola oil (LCO) blends were chemically interesterified with sodium methoxide. Changes in crystal morphology using polarized light microscopy and crystal polymorphic behavior using X-ray diffraction spectroscopy (XRD) were studied. Spherulitic crystalline particles, measuring 10–20 μm, were detected in palm oil (PO). These spherulitic particles were characterized by a dense core surrounded by a lower-density halo region. PO fat-crystal morphology was not greatly altered on addition of soybean oil (SBO), except for a gradual reduction in spherulite size as the amount of SBO in the blends was increased. Chemical interesterification (IE) did not alter PO or POSBO blend fat-crystal morphology significantly. Irregular particles and spherulites of different sizes and shapes were observed in lard, from small crystals to irregular, angular crystal aggregates. Changes in lard fat-crystal morphology due to the addition of canola oil (CO) were concentration-dependent. In general, spherulite diameter decreased with increasing CO addition. IE dramatically altered lard fat-crystal morphology—IE induced the formation of more symmetrical spherulitic crystalline particles, and the halo-to-core ratio was increased significantly. XRD spectroscopic analysis of POSBO blends revealed small changes in the long spacings of PO fat crystals with either blending or IE; all values were close to 45 ?. Short spacings of fat crystals in noninteresterified (NIE) POSBO blends suggested the predominance of β′ polymorphs. IE led to an increase in the proportion of the β polymorph in PO and POSBO blends. Long spacings of NIE lard fat crystals suggested the presence of a bilayer structure in their unit cells (45 ?). Dilution with ≥10% canola oil led to the appearance of a second reflection at 35 ?. β′ polymorphs were predominantly detected in NIE lard and NIE LCO blends. The β polymorph became more evident with increasing addition of CO. Fat crystals in IE lard and IE LCO blends displayed a single long-spacing reflection at 40 ?. IE of lard and LCO blends induced the formation of β polymorphs.     

Identification of CYP106A2 as a regioselective allylic bacterial diterpene hydroxylase

The cytochrome P450 monooxygenase CYP106A2 from Bacillus megaterium ATCC 13368 catalyzes hydroxylations of a variety of 3-oxo-Δ(4) -steroids such as progesterone and deoxycorticosterone (DOC), mainly in the 15β-position. We combined a high-throughput screening and a rational approach for identifying new substrates of CYP106A2. The diterpene resin acid abietic acid was found to be a substrate and was docked into the active site of a CYP106A2 homology model to provide further inside into the structural basis of the regioselectivity of hydroxylation. The products of the hydroxylation reaction were analyzed by HPLC and the V(max) and K(m) values were calculated. The corresponding reaction products were analyzed by NMR spectroscopy and identified as 12α- and 12β-hydroxyabietic acid. CYP106A2 was therefore identified as the first reported bacterial cytochrome P450 diterpene hydroxylase. Furthermore, an effective whole-cell catalyst for the selective allylic 12α- and 12β-hydroxylation was applied to produce the hydroxylated products.     

The influence of surface defects on ethanol dehydrogenation versus dehydration on the UO2(1 1 1) surface

The decomposition of ethanol has been investigated on Ar⁺-sputtered surfaces of a UO₂(1 1 1) single crystal. X-ray photoelectron spectroscopy (XPS) of the U 4f peaks after sputtering for 1 h showed the presence of two distinct oxidation states: U⁴⁺ (U 4f_7/2 at 380.2 eV) and U⁰ (U 4f_7/2 at 377.4 eV). Upon ethanol exposure at room temperature, the peak at 377.4 eV was attenuated, indicating that U⁰ sites were oxidized to U^x+i(x≤4). The presence of a mixture of oxidation states on the surface influenced the reaction products observed during temperature programmed desorption (TPD). While ethylene and acetaldehyde desorbed in one temperature domain (at 560 K) from stoichiometric UO₂(1 1 1), an additional desorption domain (at 475 K) was observed over the substoichiometric surface. The ratio of acetaldehyde to ethylene produced was different in the two temperature domains. While this ratio was near unity for the 560 K domain, it decreased to ca. 0.5 for the 475 K peaks on the substoichiometric surface. The lower temperature reaction channel is likely associated with surface oxygen vacancies, as it leads to greater oxygen abstraction, forming ethylene from surface ethoxide species.     

Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening

Inhibition of cytochrome P450 (CYP) is a major cause of herb-drug interactions. The CYP1A2 enzyme plays a major role in the metabolism of drugs in humans. Its broad substrate specificity, as well as its inhibition by a vast array of structurally diverse herbal active ingredients, has indicated the possibility of metabolic herb-drug interactions. Therefore nowadays searching inhibitors for CYP1A2 from herbal medicines are drawing much more attention by biological, chemical and pharmological scientists. In our work, a pharmacophore model as well as the docking technology is proposed to screen inhibitors from herbal ingredients data. Firstly different pharmaphore models were constructed and then validated and modified by 202 herbal ingredients. Secondly the best pharmaphore model was chosen to virtually screen the herbal data (a curated database of 989 herbal compounds). Then the hits (147 herbal compounds) were continued to be filtered by a docking process, and were tested in vitro successively. Finally, five of eighteen candidate compounds (272, 284, 300, 616 and 817) were found to have inhibition of CYP1A2 activity. The model developed in our study is efficient for in silico screening of large herbal databases in the identification of CYP1A2 inhibitors. It will play an important role to prevent the risk of herb-drug interactions at an early stage of the drug development process.     

Quantum effects at TSCC1-xBx monocrystals: The influence of an external electric field on the permittivity peak

The results of model calculations and of experimental investigations of the shift of the temperature T_M of the maximum of the permittivity ε_b due to an external electric d.c. field on tris-sarcosine calcium chloride_1-x bromide_x (TSCC_1-xB_x) monocrystals with different concentrations x are described. It is shown that in the low temperature region a marked enhancement of the response of the permittivity maximum to an external electric d.c. field is caused by quantum effects.     

The effects of a high dosage of creatine and caffeine supplementation on the lean body mass composition of rats submitted to vertical jumping training

Background  

The influences of creatine and caffeine supplementation associated with power exercise on lean body mass (LBM) composition are not clear. The purpose of this research was to determine whether supplementation with high doses of creatine and caffeine, either solely or combined, affects the LBM composition of rats submitted to vertical jumping training.     

The influence of hydrodynamic and mass transfer entrance effects on the operation of a parallel plate electrolytic cell

Experimental measurements of mass transfer in an electrochemical flow cell of rectangular cross section with different hydrodynamic entrance and electrode lengths have been made. For fully developed flow, average Sherwood numbers under laminar conditions vary with Graetz number to a power 0·30. For turbulent flow, fully developed mass transfer conditions occur about twelve equivalent diameters along the electrode and are best represented by the Chilton-Colburn analogy which predicts Sherwood numbers varying with Reynolds number to a power of 0·8 and Schmidt number to a one-third power. For shorter electrodes Sherwood numbers can be adequately correlated by an expression with Reynolds number to a two-thirds power and dimensionless electrode length to a power of −0·2. For hydrodynamic entrance lengths of not less than eight equivalent diameters, data in the laminar region can be expressed by an emperical boundary layer type of equation which includes terms for the hydrodynamic entrance length and electrode length. In the turbulent regime substantially developed flow occurs after eight entrance lengths and correlations with fully developed flow equations are satisfactory     

Synthesis and in vitro Activity of Heterocyclic Inhibitors of CYP2A6 and CYP2A13, Two Cytochrome P450 Enzymes Present in the Respiratory Tract

To be sniffed at : Several 1‐ and 2‐substituted 1H‐imidazoles and 2‐substituted oxazoles, oxazolines and pyrazines have been synthesized and tested as inhibitors of the cytochrome P450 enzymes CYP2A6 and CYP2A13. 1‐Substituted 1H‐imidazoles bearing short chains (pentyl, hexyl or hexenyl) were found to be potent inhibitors of both enzymes, and showed IC₅₀ values of about 2 μM .

     

TiO2对聚氯乙烯紫外光稳定与催化降解的影响

综述了普通和纳米TiO_2对聚氯乙烯(PVC)的紫外光稳定和催化降解的机理及研究进展,以及包覆和掺杂改性对TiO_2光稳定和光催化性能的作用。金红石型纳米TiO_2具有优异的紫外光稳定特性,锐钛型纳米TiO_2表现出极强的光催化活性。无机包覆过的金红石型TiO_2对PVC有明显的保护作用。有机改性则能提高锐钛型TiO_2的分散性,从而提高其对聚合物的光催化效率。过渡金属离子掺杂可在TiO_2晶格中引入缺陷位置或改变结晶度,从而改变PVC的光降解速率。     

The influence of irradiation on the microhardness and photoluminescence of SiO2

The microhardness and photoluminescence spectra excited with 337-nm laser radiation in commercial SiO₂ glasses (UV windows, substrates with BaTiO₃ film coatings) exposed to ⁶⁰Co gamma radiation and a mixed neutron flux from the reactor are investigated. It is revealed that initial samples contain nanocrystalline phases. An increase in the microhardness and the intensity of the excitonic UV luminescence due to ⁶⁰Co gamma irradiation and the quenching of the photoluminescence associated with the nonbridging oxygen centers result from healing of Si-O dangling bonds and microcracks in the surface layer at the nanocrystal-glass matrix and substrate-coating interfaces. It is demonstrated that reactor irradiation leads to the phase transformation of SiO₂ cristobalite into tridymite and BaO into BO₂, as well as to the decomposition of BaTiO₃ and BaCO₃. This brings about a decrease in the microhardness and photoluminescence quenching.     

The influence of the processing parameters on the reactive flash sintering of ZrO2-CeO2

Reactive flash sintering (RFS) is a method that was recently developed to produce dense single-phase bulk ceramic parts through solid-state reactions in a single-step that only takes a few minutes. The influence of the RFS parameters on the phase purity of a simple mixed oxide, (Zr_0.8,Ce_0.2)O₂, was investigated. Parameters such as furnace temperature, furnace atmosphere, electric current density, and alternating current (AC) or direct current (DC) were examined. It was found that (Zr_0.8,Ce_0.2)O₂ pellets with high densities, above 90% of its theoretical density, can be produced by RFS in a few minutes when RFS occurs under oxidizing atmospheres, AC fields with current densities of 100 mA·mm⁻², and at a furnace temperature of 1200°C. Reducing conditions such as Ar-H₂ atmosphere and DC fields, low furnace temperatures, and low current densities resulted in phase impurities and poor reactions between the ZrO₂ and the CeO₂ powders. These results show that RFS is a useful method to produce mixed oxides, but it is very sensitive to the processing parameters. This is the first time that the influence of most of the RFS processing parameters has been studied systematically. Thus, the present work aims to provide guidelines on selecting the right processing parameters when exploring RFS.     

The influence of CNTs on the thermoelectric properties of a CNT/Bi2Te3 composite

CNT/Bi₂Te₃ composites were prepared from composite powders in which CNTs were implanted in the Bi₂Te₃ matrix powders by a novel chemical route. It was found that the fabricated composite had a microstructure of a homogeneous dispersion of CNTs in the Bi₂Te₃ matrix due to interfacial bonding agents of oxygen atoms attaching to the surface of CNTs. The dimensionless figure of merit (ZT) of the composite shows significantly increased values compared to those of pure binary Bi₂Te₃ in the temperature range of 298–498 K and a maximum ZT of 0.85 was obtained at 473 K. It is considered that the improved thermoelectric performance of the composite mainly originated from thermal conductivity that was reduced by active phonon-scattering at the CNT/Bi₂Te₃ interface.     

The Oxidation of Hydrophobic Aromatic Substrates by Using a Variant of the P450 Monooxygenase CYP101B1

The cytochrome P450 monooxygenase CYP101B1, from a Novosphingobium bacterium is able to bind and oxidise aromatic substrates but at a lower activity and efficiency than norisoprenoids and monoterpenoid esters. Histidine 85 of CYP101B1 aligns with tyrosine 96 of CYP101A1, which, in the latter enzyme forms the only hydrophilic interaction with its substrate, camphor. The histidine residue of CYP101B1 was mutated to phenylalanine with the aim of improving the activity of the enzyme for hydrophobic substrates. The H85F mutant lowered the binding affinity and activity of the enzyme for β-ionone and altered the oxidation selectivity. This variant also showed enhanced affinity and activity towards alkylbenzenes, styrenes and methylnaphthalenes. For example the rate of product formation for acenaphthene oxidation was improved sixfold to 245 nmol per nmol CYP per min. Certain disubstituted naphthalenes and substrates, such as phenylcyclohexane and biphenyls, were oxidised with lower activity by the H85F variant. Variants at H85 (A and G) designed to introduce additional space into the active site so as to accommodate these larger substrates did not improve the oxidation activity. As the H85F mutant of CYP101B1 improved the oxidation of hydrophobic substrates, this residue is likely to be in the substrate binding pocket or the access channel of the enzyme. The side chain of the histidine might interact with the carbonyl groups of the favoured norisoprenoid substrates of CYP101B1.     

The inhibition effect of 20(S)-Protopanaxadiol (PPD) and Ginsenoside Rh2 for CYP2C9 and CYP3A4

With the aid of the automated molecular docking, the inhibition effect of 20(S)-Protopanaxadiol (PPD) and Ginsenoside Rh2 for CYP2C9 and CYP3A4, respectively, were studied by InsightII/Affinity program and the docking complexes were analyzed by InsightII/Ludi program. The results indicate that PPD is a competitive inhibitor for CYP2C9 but a poor inhibitor for CYP3A4, Rh2 is a noncompetitive inhibitor for CYP3A4, but a poor inhibitor for CYP2C9. Hydrophobic PPD is stabilized in the center of the substrate-binding regions of CYP2C9 by hydrogen bond and has strong interactions with heme and the key residues in active site which play important role for binding the substrate. Theoretical K_i value was calculated to be 26.7 μM by using Ludi score 457 of CYP2C9-PPD complex. As hydrophilic Rh2 is away from the substrate-binding regions of CYP3A4, it has very weak interactions with the key residues in the active site. But the docking of Rh2 makes the conformation of CYP3A4 to change, including the position of a key residue Ser119 that leads to a decrease in catalytic activity. Theoretical K_i value is 102.8 μM by using Ludi score 398 of CYP3A4-Rh2 complex. The theoretical results are in well agreement with the experimental results.     

The influence of processing methods on the dielectric properties of BaTi1-xGdxO3-x/2 - Based materials

In this study, the intermediate rare-earth oxide Gd₂O₃ (Gd) was substituted in different amounts (x = 0.2–2 mol%) for the formulation of BaTi_1-xGd_xO_3-x/2 (BTG_x) dielectric materials. The effect of B-site substitution was confirmed by the additional Raman active A_1g octahedral peak at ~835cm^-1 strengthened at x ≥ 0.4 mol%. Additionally, properties of 0.9BTG_0.007-0.1BA dielectric ceramics were analysed based on the influence of various processing methods as a function of sintering temperature. The focal samples were labelled Method-A (direct-mix) and Method-B (indirect-mix). As the sintering temperature (1075–1200 °C) increased, the 1 kHz response of the ε–T curves of Method-A samples transformed from a single peak to broad-narrow double peaks of high dielectric loss tangent (tan δ). Nonetheless, samples of Method-B possessed a clearly defined transmission electron microscopy (TEM) core-shell structure, flattened double-peak ε-T curves, optimised dielectric properties (ε = ~1563–1851 and tan δ < 1.5% at room temperature), and a wide-ranging temperature behaviour that meets the X8R dielectric standards (ΔC/C_25°C < ±15%). The maximum dielectric breakdown strength of Method-B samples reached ~131 kVcm, while the energy storage density was ~0.726 J/cm³ at a maximum efficiency of ~80% at 1100 °C. Thus, exhibiting good potentials for balancing temperature stability with energy storage applications.